Mitotic crossing over is detrimental because it can lead to loss of heterozygosity or chromosome rearrangement, both of which are associated with cancer. The dangers of mitotic crossing over are evident in persons with Bloom syndrome, a rare, hereditary disease characterized by a highly elevated incidence and early onset of a broad range of malignancies. A predominant feature of cells from these patients is elevated mitotic crossing over between sister chromatids, homologous chromosomes, and heterologous chromosomes. Studies of BLM, which encodes a RecQ helicase, are providing important insights into mechanisms cells use to prevent mitotic crossing over. We are contributing to these insights by exploiting unique advantages of Drosophila as a model metazoan for genetic and molecular studies of the cellular functions of the BLM helicases. We have developed a detailed model for the function of Drosophila BLM in double-strand break repair, and will test predictions of this model, as well as alternative models proposed by others. Since DmBLM is only one component of one pathway that prevents mitotic crossing over, we will take physical and genetic approaches to identifying other proteins and genes that have important anti-crossover functions. These studies will enhance our understanding of mechanisms of mitotic crossing over and the role that the important tumor suppressor protein BLM plays in preventing mitotic crossing over.